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Completed

NCT Number: NCT03489993

FGF23 and Angiotensin-(1-7) in Hypophosphatemia (GAP)

Hereditary hypophosphatemia encompasses rare genetic conditions characterized by renal phosphate wasting. Increased circulating levels of fibroblast growth factor 23 (FGF23), a key regulator of phosphorus metabolism, are critical to the pathophysiology of these diseases, most notably in X-linked hypophosphatemia (XLH). Increased FGF23 induces hypertrophy and scarring in the heart in part via stimulating the traditional renin-angiotensin system (RAS) pathway, angiotensin-converting enzyme (ACE)/angiotensin (Ang ll), particularly in patients with chronic kidney disease, but the effect of FGF23 on the heart in patients with FGF23-related hypophosphatemic diseases is unknown. In addition, the relationship between FGF23 and the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1-7) (Ang-(1-7) pathway of the RAS is unknown.

The objective of this study is to describe the relationship between FGF23, which causes low phosphorus levels, and components of the RAS in the blood and urine to help the investigators understand why the disease occurs and how to better treat it.

Subjects will be identified by querying the Electronic Medical Record according to medical diagnosis. Thirty subjects, 2-24 years of age, will be recruited from the tertiary care Pediatric Endocrinology and Pediatric Nephrology clinics at Brenner Children's Hospital. Inclusion criteria include a confirmed diagnosis of hereditary FGF23-related hypophosphatemia. Clinical data will be obtained from the Electronic Medical Record. Each subject will undergo study assessments at baseline, 6 months and 1 year that include blood work, an echocardiogram, and blood pressure measurements.

The primary hypothesis is that subjects with higher Ang-(1-7) levels have lower rates of cardiac hypertrophy and thus are protected against high FGF23 levels. The secondary hypothesis is that subjects with higher Ang-(1-7) levels have lower systolic blood pressure.

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Key information

Conditions

Hypophosphatemia Avitaminosis Bone Diseases Bone Diseases, Metabolic Calcium Metabolism Disorders Cardiomegaly Cardiovascular Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Deficiency Diseases Familial Hypophosphatemic Rickets Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Heart Diseases Hypertrophy Hypertrophy, Left Ventricular Hypophosphatemia, Familial Kidney Diseases Left Ventricular Hypertrophy Male Urogenital Diseases Malnutrition Metabolic Diseases Metabolism, Inborn Errors Metal Metabolism, Inborn Errors Musculoskeletal Diseases Nutrition Disorders Nutritional and Metabolic Diseases Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Phosphorus Metabolism Disorders Renal Tubular Transport, Inborn Errors Renin-angiotensin System Rickets Rickets, Hypophosphatemic Urogenital Diseases Urologic Diseases Vitamin D Deficiency X-linked Hypophosphatemia

Age range

2 year–24 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

About this study

Clinical data will be collected from the Electronic Medical Record, including age, sex, parent-reported race, past medical and family histories, and current medications. The investigators will calculate body mass index and define overweight/obesity as a body mass index ≥85% percentile for age and sex. The investigators will calculate the estimated glomerular filtration rate to measure renal function based on serum creatinine standardized to age, sex, and height.

Blood (less than 5 mL) and urine samples will be collected at each study visit at the same time as routine clinical labs. Ang ll and Ang-(1-7) will be measured in the plasma and urine using radioimmunoassays in a CLIA-certified laboratory within the Hypertension and Vascular Research Biomarker Analytical Core at Wake Forest School of Medicine. The investigators will calculate the ratio of the two peptides and, in the urine, standardize their values to urine creatinine. In the blood, creatinine, calcium, phosphorus, and vitamin D will be collected and in the urine, albumin, calcium, phosphorus, and creatinine will be collected all per standard of care. FGF23 and klotho will be analyzed in the Core via commercially available ELISA's.

All patients receive baseline and, if abnormal, follow-up echocardiograms to evaluate for left ventricular hypertrophy.

Blood pressure will be measured at clinic visits. Because age, sex, and height define normative pediatric values, the investigators will standardize blood pressure with z scores.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Confirmed diagnosis of hereditary FGF23-related hypophosphatemia

Exclusion criteria

  • Acquired FGF23-related hypophosphatemia
  • Age less than 2 years
  • Age more than 24 years
  • Inability to provide urine sample

Treatment and study plan

Ang II and Ang-(1-7)

Diagnostic Test

Measured in plasma and urine using radioimmunoassays.

FGF23 and klotho

Diagnostic Test

Measured using ELISA's.

Primary outcomes

  1. Left ventricular hypertrophy

    Time frame: 1 year

    Higher Ang-(1-7) levels will be associated with a decreased rate of left ventricular hypertrophy

Secondary outcomes

  1. High blood pressure

    Time frame: 1 year

    Higher Ang-(1-7) levels will be associated with lower systolic blood pressure

Sponsors and collaborators

Lead sponsor

Wake Forest University Health Sciences

Other

Registry information

Official study title

Interplay of FGF23 and Angiotensin-(1-7) in Hypophosphatemia (GAP)

Acronym: GAP

Important dates

Study start
2018
Primary completion
2020
Study completion
2020
First posted
Apr 6, 2018
Registry last updated
Aug 5, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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